Successful allogeneic SCT in infant with FHL,

dilemmas in using „unaffected“ sibling

P.Sedláček, R. Špíšek, et al

2nd Medical School,

Charles University, Prague, CZESID – May 10.-11. 2004

Past Medical History (family)

• mother HBsAg +, no transf.history

• father – OK

1st girl – died 32nd gest.week (umb. cord problems)

2nd boy (IVF) – Jakub – alive/well

3rd girl (IVF) - Jana * July 8th 2003

History of Present Illness I

– early postnatal pancytopenia

(WBC : 4,8, RBC: 3,1, ret.: 0,1%, ANC: <100, Plt 11)

allo HLA Ab in mother

exchange transfusion (D+9), PRBC, Plt, Fbg

HSmegaly, hepatopathy, hypertriglycemia, hyperbilirubinemia

hyperferritinemia ( >18 000)

DIC, infections, fever and elev. CRP,

HBsAg and HBeAg negative (Engerix, Hepatect)

Admission to our department at the age of 28 days (Aug.2003)

History of Present Illness II

• Day of admission Aug. 5th 2003

– liver +4cm, spleen +3-4cm bcm, pancytopenia

• Therapy according to HLH 94

– (VP16, Dexa, CsA)

– discontinued for acute sepsis

• Transfusion history pre SCT

– PRBC 13 x (or more)

– Plt more than 13

Pre-transplant condition

• HSmegaly, ferritin 3153

• antiHBc and antiHBe pos., HBsAg neg.

• Failure to thrive (bw 3,45 kg; 2,8 kg at birth)

• normal LFT; Plt 100, WBC and RBC normal

• brother fully HLA matched, 19kg bw, 3yo

• ABO incompat. : A+ vs. B- (low titers)

Diagnostics-1FACS analysis of perforin expression in NK cellsExclusion of FHL type 2- perforin deficiency

100 101 102 103 104

FL2-H: PERFORIN

0

20

40

60

80

100

% o

f Ma

x

100 101 102 103 104

FL2-H: PERFORIN

0

20

40

60

80

100

% o

f Ma

x

Patient´s NK cellsControl

87% of NK 87% of NK cells are cells are perforin +perforin +

87% of NK 87% of NK cells are cells are perforin +perforin +

Brother´s NK cells

Control

Diagnostics-2• Cytotoxic activity of T-lymphoblasts generated from T-cells• Target cells: L1210 cells deficient in FAS expression

0

10

20

30

40

50

60

70

80

60:1 30:1 6:1 1,2:1 0,2:1

% c

ytot

oxic

ity

patient

brother

control

• defective cytotoxic activity of patient´s lymphoblasts

• normal findings in her brother donor of SCX

Transplantation

• 11.9.2003 (* 8.7.2003)• Bu(19mgkg) + Cy(200) + rATG(25mg/kg)• CsA + MP (MTX not used due to early and severe VOD)

• BM : NC : 8,9x 108/kg; CD34: 22x106/kg• VOD : D+1 (D-3 through D+15 defibrotide)

– Bilirubinemia, thrombocytopenia, ascites, ARDS

• Engraftment :ANC (500) D+19; Plt (20/50) D+22/+26• Chimer. : stable, 95% donor• Discharched to outpatient clinic D+34• no aGVHD, no cGVHD so far (~D+240)

– continues on CsA, steroids D/C ~D+50– growth catch-up

Acknowledgement

• Department of Pediatric Hematology and Oncology– HSCT unit; Division of Hematology

• Institute of Immunology– diagnostics of primary HLH

• Institute of Hematology and Blood Transfusion– HLA typing